'Born in Michigan? You're in the biobank': engaging population biobank participants through Facebook advertisements.

BACKGROUND/AIMS: Despite a broad call for biobanks to use social media, data is lacking regarding the capacity of social media tools, especially advertising, to engage large populations on this topic. METHODS: We used Facebook advertising to engage Michigan residents about the BioTrust for Health. We conducted a low-budget (

C-fos expression in vivo in human lymphocytes in response to stress.

1. Blood samples from which lymphocytes were isolated were obtained from patients immediately prior to cardiac catheterization (stress period) and again four to five hours later (post-stress period). Blood was also taken from a normal non-stressed control subject. 2. Lymphocyte c-fos mRNA was reverse transcribed followed by strand synthesis of DNA template and amplification using PCR with sequence-specific primers. 3. C-fos mRNA was detectable in lymphocytes from the normal control subject and in patient samples obtained immediately prior to cardiac catheterization, but was not detectable in patient samples obtained four to five hours later. 4. Possible mechanisms for these findings include a stress-related decrease in lymphocyte proliferation and differentiation or a negative feedback effect of the c-fos protein on transcription of the c-fos gene. 5. These findings suggest that it may be possible to monitor peripheral early gene expression as a marker for a variety of conditions including stress, psychiatric disorders and the response to psychotropic drugs.

The use of ubiquitin as a marker of thyroxine-induced apoptosis in cultured Rana catesbeiana tail tips.

Cultured Rana catesbeiana tadpole tail tips were used in combination with a fluoroimmunoassay to determine the levels of ubiquitin--a protein marker of programmed cell death in other systems--during the tissue regression induced by thyroxine (T4). After a 3-day pretreatment with the hormone, tail tips cultured in T4 showed significant increases in ubiquitin levels by 48 hr. Tail tips taken from tadpoles that had been immersed in T4 for 6 days showed a parallel increase in ubiquitin levels, demonstrating the same change in vivo. Treatment of cultured tail tips with the protein kinase C inhibitor, H-7, blocks both regression and the rise in ubiquitin seen in tips treated with T4 alone. Treatment of cultured tips with T4 and either cycloheximide or actinomycin D inhibits regression compared to T4 alone; however, the rise in ubiquitin is only blocked by cycloheximide, suggesting that ubiquitin is being made from RNA that was synthesized during the pretreatment period or earlier. These results suggest that ubiquitin will serve as a good molecular marker of tissue regression in the T4-treated tadpole tail and that it will be productive to consider tissue regression during amphibian metamorphosis as a specific case of programmed cell death or apoptosis.

Inhibition of protein kinase C antagonizes in vitro tadpole tail fin regression induced by thyroxine.

Tail fin regression can be induced in anuran amphibians with L-thyroxine (T4). This regression can be antagonized with prolactin (PRL). Previous work had suggested that protein kinase C (PKC) was involved in PRL action. To address this issue further, the effect of a potent and selective inhibitor of protein kinase C on in vitro tail fin regression was investigated. T4-induced regression of tail fin pieces from Rana pipiens tadpoles could be antagonized by adding PRL or the PKC inhibitor H-7 to the medium. H-7 inhibited fin regression in a dose-dependent manner, with a half-maximal effective concentration of about 10(-5) M. The H-7 analogue, HA-1004 (which is not a selective inhibitor of PKC), was without effect. These results suggest a possible role for PKC in tail fin regression and may be useful in elucidating the antimetamorphic action of PRL.

Reduced calcium and inhibition of protein kinase C mimic the enhancement of ornithine decarboxylase activity of prolactin in Ambystoma tigrinum tissues.

We previously reported that prolactin (PRL) could increase the activity of ornithine decarboxylase (ODC) in liver slices taken from larval tiger salamanders (Ambystoma tigrinum). This action of the hormone was inhibited by oxytocin (OT), the calcium ionophore A23187, and diacyglycerol (DG) and was duplicated by 10 microM verapamil (VML), a calcium channel blocker. Here, we expand these results to show that 1) a higher dose of VML (50 microM) produces an additive effect with PRL; 2) addition of small amounts of calcium (0.1 mM) to the liver culture medium blocks PRL action; 3) neither nifedipine (NIF), a different type of calcium channel blocker, nor EDTA alter PRL action; and 4) gossypol, a reported inhibitor of protein kinase C, mimics PRL action. Additionally, we show that PRL increases ODC activity in tiger salamander tail skin in vitro, a tissue previously demonstrated to be a PRL target tissue in this species. The same set of treatments which we have shown to modify PRL effects on ODC in liver slices affects PRL action in the tail skin in a parallel manner. Thus, the mechanism whereby PRL enhances ODC activity appears to be the same in both these tissues. These results are discussed in conjunction with the findings from similar studies using mammalian tissues in an attempt to assess the current picture of the mechanism of PRL action and the possible role of inositol phospholipid turnover, calcium, and protein kinase C in the action of this hormone.

Enhancement of ornithine decarboxylase activity in Ambystoma liver slices by ovine prolactin: an evaluation of possible mediators.

Prolactin has been shown to increase the activity of ornithine decarboxylase in a variety of mammalian tissues and in the pigeon crop sac. This study demonstrates a similar effect of ovine prolactin on ornithine decarboxylase activity in liver slices taken from larval tiger salamanders (Ambystoma tigrinum). An evaluation of potential mediators of prolactin action in liver slices revealed that the effect of the hormone on enzyme activity was not blocked by ouabain, an inhibitor of the sodium pump reported to block other actions of prolactin. Oxytocin, which inhibits prolactin actions in A. tigrinum, blocked the increase in ornithine decarboxylase activity induced by prolactin. Since previous results had implicated inositol phospholipid turnover in oxytocin action, the effects of the calcium ionophore, A 23187, and of synthetic diacylglycerol were examined. Both agents blocked the increase in enzyme activity when they were combined with prolactin treatment. Verapamil, a calcium channel blocker, had a prolactin-like effect on the activity of ornithine decarboxylase, and the combination of prolactin and verapamil produced a stimulation of the enzyme that was no greater than that observed with either the drug or prolactin alone, suggesting that both agents might be acting via a common cellular pathway. The tentative hypothesis that prolactin acts via a mechanism which lowers intracellular calcium is suggested.

Effects of prenatal exposure to neuroleptic drugs on children's growth.

The effect of prenatal exposure to neuroleptic drugs on height and weight from birth to 7 years was examined in children of psychiatrically normal parents and of parents with a history of psychiatric treatment, using data from the Collaborative Perinatal Project of the National Institute of Neurological Diseases, Communicative Disorders, and Stroke. Analysis of covariance was used to control for potential confounding factors. We found that prenatal exposure to dopamine receptor-blocking neuroleptic drugs was associated with increased height in one or more of our groups at 4 months, 1 year, and 7 years and less consistently with increased weight. Seven-year-old children who had been exposed to these drugs for more than 2 months during gestation were approximately 3 cm taller than unexposed controls (p less than 0.05). Prenatal exposure to dopamine-depleting agents was associated with decreased height at 4 months but not later. Possible mechanisms for these effects, including a permanent decrease in the number of brain dopamine receptors and effects on various hormones, are discussed.

Effect of repeated restraint stress, desmethylimipramine or adrenocorticotropin on the alpha and beta adrenergic components of the cyclic AMP response to norepinephrine in rat brain slices.

The cyclic AMP response to catecholamines in rat cortical slices is mediated by a beta adrenergic receptor which is coupled to adenylate cyclase and an alpha adrenergic receptor which potentiates the response to beta receptor stimulation. The present studies examined the effects of repeated restraint stress, adrenocorticotropin or desmethylimipramine administration on the beta and alpha adrenergic components of this response. Restraint was found to produce a small nonsignificant decrease of the beta receptor response accompanied by a significant reduction of the alpha receptor-induced potentiation of the beta response. Desmethylimipramine was found to lower the cyclic AMP response to beta receptor stimulation but not to alter the alpha-induced potentiation of the beta response. Adrenocorticotropin, like restraint stress, was found to reduce only the alpha-induced potentiation of the beta response. Experiments with adenosine and histamine showed that restraint stress lowered the alpha-induced potentiation of cyclic AMP responses to these neurohormones also. It is concluded that restraint stress acts primarily to reduce the response to stimulation of central alpha adrenergic receptors whereas desmethylimipramine acts primarily to reduce the response to stimulation of beta adrenergic receptors. Adrenocorticotropin has the same effect as restraint stress suggesting that pituitary adrenal hormones mediate the stress effect.

Antagonistic effects of prolactin and oxytocin on tail fin regression and acid phosphatase activity in metamorphosing Ambystoma tigrinum.

We have found that the inhibition of thyroxine-induced tail fin regression by prolactin in larval tiger salamanders is antagonized by oxytocin. Other workers have shown that prolactin blocks the rise in activity of several hydrolytic enzymes that occurs in regressing tissue during metamorphosis. Here, we examine the effects of prolactin and oxytocin--given alone and in combination--on tail fin regression and acid phosphatase specific activity in this tissue. Both long-term (12-day) and short-term (48-hr) treatment paradigms using prolactin and oxytocin are investigated. The results show that long-term prolactin treatment of metamorphosing larvae blocks fin regression and the rise in acid phosphatase specific activity seen in metamorphosing controls; short-term prolactin treatment of metamorphosing larvae inhibits fin regression within 48 hr, but does not block the rise in acid phosphatase activity seen in controls; oxytocin antagonizes the effects of prolactin on tail fin regression; and oxytocin treatment (long-term or short-term) of metamorphosing larvae causes an elevation of acid phosphatase activity above that seen in metamorphosing controls. With long-term treatment, this effect of oxytocin is slightly antagonized by prolactin; with short-term treatment, no antagonism is observed even though an effect of prolactin on fin height is still evident. We have interpreted these results as suggesting that the effect of prolactin on hydrolase activity is not a prerequisite for its inhibitory effect on fin regression to occur.

Reduction of the cyclic adenosine 3',5'-monophosphate response to catecholamines in rat brain slices after repeated restraint stress.

Restraint stress reduces the cyclic AMP (cAMP) response to norepinephrine (NE) in slices of the rat cerebral cortex and hypothalamus. This effect is found after repeated but not single exposure to stress and persists for at least 24 hr poststress. The magnitude of the reduction is dose-dependent in that greater decreases are found after higher frequencies and longer durations of restraint as well as after more disturbance during the stress. Analysis of the NE-cAMP dose-response curve indicates that the stress reduces the maximum cAMP response to NE but does not increase the EC50 value of NE. The cAMP response to isoproterenol is only slightly affected by the stress. No effect is observed on specific [3H]dihydroalprenolol binding in either brain region at 24 hr poststress. These results suggest that repeated restraint stress produces a selective persistent reduction of the function of brain non-beta adrenergic receptors. This effect may be mediated by an increased release of adrenocorticotropic hormone as chronic infusion of the latter hormone mimics the action of stress on cAMP responses to catecholamines. An increased release of brain NE may also be involved as repeated administration of the NE-reuptake inhibiting antidepressant, desmethylimipamine, reduces the function of non-beta as well as beta adrenergic receptors as evidenced by reductions of both the NE- and isoproterenol-cAMP responses.

Cognitive effects of lithium carbonate and haloperidol in treatment-resistant aggressive children.

The effects of lithium carbonate and haloperidol on cognition were examined in a placebo-controlled, double-blind study of 61 treatment-resistant, hospitalized school-aged children. They all had a DSM-III diagnosis of conduct disorder-- undersocialized , aggressive, with a profile of highly explosive and aggressive behavior. Children were assessed at the end of a two-week placebo-baseline period and again after four weeks of treatment. Drug effects on cognition were mild. Haloperidol (mean dose, 2.95 mg/day) caused significant decreases in Porteus Maze test quotient scores and a slowing of reaction time (RT) on a simple RT task. Lithium carbonate (mean dose, 1,166 mg/day) adversely affected qualitative scores on the Porteus Maze test. No significant treatment effects were found for the Matching Familiar Figures Test, short-term recognition memory and concept attainment tasks, or the Stroop Test.

Reduction of the cAMP response to norepinephrine in rat cerebral cortex following repeated restraint stress.

The present studies examined the effect of restraint stress on the sensitivity of the catecholamine-cAMP generating system in the rat cerebral cortex. Restraint was found to cause a persistent reduction in the magnitude of the cAMP response to catecholamines. This effect occurred after repeated but not acute stress and was more marked with twice-daily as compared to once-daily treatment. The reduction in response was more marked with norepinephrine than with isoproterenol, indicating a selective action of stress on the non-beta component of the noradrenergic response. The findings suggest that subsensitivity of the cAMP response to norepinephrine is a general response to chronic stressful stimuli and may be related to the action of certain antidepressant agents.

The effect of acute and chronic administration of desmethylimipramine on responses to stress in rats.

Rats were given single or repeated injection of desmethylimipramine (DMI) and subjected to a single session of restraint or footshock stress. The degree of anorexia and plasma corticosterone elevation in response to the stress was measured. Repeated but not single injection of DMI was found to reduce the anorectic response to restraint and footshock but not to affect the corticosterone response to restraint. It is concluded that repeated DMI treatment has differential effects on responses to acute stress.

Chronic restraint stress elicits a positive antidepressant response on the forced swim test.

The present study investigated behavioral parallels between adaptation to stress and antidepressant treatment using the forced swim test. Restraint stress given repeatedly for 11 days significantly reduced immobility on this test. A single application of stress had no effect. The reduction in immobility produced by repeated restraint was quantitatively similar to that produced by repeated administration of desmethylimipramine. These results confirm previous findings of similarities in the behavioral and neurochemical response to chronic stress and chronic antidepressant treatment.

Brain adrenergic receptors and resistance to stress.

The relationship between brain beta-adrenergic receptors and adaptation to stress was studied in rats subjected to repeated restraint stress. The stress was found to produce a reduction in the density of these receptors in the hypothalamus, cerebral cortex and brain stem. This change first appeared after 4-7 days and persisted for the duration of the two-week stress. Adaptation, as judged by resistance to the anorexic and gastric lesion-inducing effects of the stress, occurred progressively over the full two-week period. The loss of beta-receptors was found to correlate positively with the degree of adaptation. The relationship was strongest for the hypothalamus but was also apparent in the cortex and brain stem. These findings support the hypothesis that a reduction in the number of brain adrenergic receptors is one of the biochemical factors underlying adaptation to stress.

Effects of lithium carbonate and haloperidol on cognition in aggressive hospitalized school-age children.

A comparison of the effects of lithium, haloperidol, and placebo on cognition is reported for a sample of hospitalized school-age children with a behavioral profile of aggressiveness and explosiveness. In this double-blind study, patients were randomly assigned to one of three treatment conditions. The cognitive battery was administered at the end of a 2-week placebo baseline period and again after 4 weeks of treatment. It included a simple reaction time (RT) task with preparatory intervals of 1, 4, and 8 seconds, the Porteus Mazes, and the Matching Familiar Figures Test. Drug effects on cognition, when found, were mild. Slower and more variable RTs were found on the RT task in the haloperidol group (mean dose, 3.1 mg/day), particularly at the 4- and 8-second preparatory intervals in comparison to placebo. This appeared to reflect decreased ability to hold a preparatory set. No other effects of haloperidol on cognitive performance were found. Lithium carbonate (mean dose, 1150 mg/day) caused a deterioration in qualitative performance on the Porteus Maze Test when compared with haloperidol but had no effect on test quotient scores or on the other cognitive measures. Results are discussed in terms of dose effects and the influences of task demands. This is part of a study critically assessing the effects of lithium and haloperidol on behavioral symptoms and other parameters.